How MDMA Treats PTSD: Everything You Need to Know

This week, the U.S. Food and Drug Administration granted researchers permission to move forward with a study plan for a large-scale phase three clinical trial studying the effects of MDMA as a therapeutic drug for post-traumatic stress disorder. The news comes after the FDA reviewed the results of a years-long phase two clinical trial, backed by the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS), that showed people diagnosed with PTSD process their trauma exponentially better when under the influence of MDMA. 

That’s more progress than researchers have made with the party drug in the past. In the 1970s, doctors used MDMA as a common aid in psychotherapy, though without the FDA’s or Drug Enforcement Administration’s support. But in 1985, the same year MAPS was found, the DEA labeled MDMA a Schedule I drug, deeming it an illegal drug with no redeemable medical benefit. The fact that the FDA gave the green light without requesting additional material first is a breakthrough, one of the researchers, Dr. Michael Mithoefer, tells Rolling Stone.

But what does MDMA exactly mean for people diagnosed with PTSD? Here’s everything you need to know.

What is MDMA?
MDMA – sometimes called ecstasy or molly – is a synthetic psychoactive drug that alters mood and perception, causes euphoria and enhances pleasure. MDMA, the preferred drug of ravers, can be taken as a capsule, tablet or pill.

What’s being sold on the streets as ecstasy or molly may not actually be pure MDMA, though. According to the DEA, researchers have found much of what’s passed as MDMA contains methamphetamine, ketamine, cocaine, over-the-counter cough suppressants, diet supplements and caffeine. In fact, according to EcstasyData.org, an independent laboratory pill analysis program, 48 percent of pills sold as ecstasy tested so far this year contained only MDMA, while 10 percent had none at all. Yet just five years ago, less than 16 percent of pills sold as ecstasy contained any MDMA. “A lot of things substitute MDMA in the street drug,” says Dr. Mithoefer, who has studied the drug with support from the Multidisciplinary Association for Psychedelic Studies, a nonprofit founded in the mid-1980s.

What are MDMA’s effects on the brain?
MDMA causes the release of three neurotransmitters: norepinephrine, dopamine and, most prominently, serotonin. The release of serotonin heightens positive mood and reduces anxiety, while norepinephrine and dopamine increase energy, alertness and arousal. The synthetic drug also bumps up levels of the oxytocin and prolactin hormones, which cause a person become less receptive to fear inducers and more inclined to social interaction. An increase in prolactin, Dr. Mithoefer notes, also causes “a kind of post-orgasmic state.” That’s why most people high on ecstasy seem like horny social butterflies.

Not everyone, though, reacts the same way on MDMA. Dr. Mithoefer has seen “quite a few people” who became anxious at first before feeling any bliss. “It’s important not to get too concrete” about the effects, he says, “because it’s a complicated interaction.”

How does MDMA help treat PTSD?
People diagnosed with PTSD may become besieged by emotion or far removed from their feelings when reprocessing their trauma. That makes it difficult for them to work through their trauma effectively, even when the process is painful. MDMA, on the other hand, gives a person some time to work through their traumatic memories “without being overwhelmed and without being emotionally numb,” said Dr. Mithoefer. “It’s an interesting state.”

He calls this phase “the optimal arousal zone.” It happens because MDMA decreases activity in the amygdala – the almond-shaped part of the brain that perceives threats – and increases activity in the prefrontal cortex – the region that controls behavior, personality and decision-making. That allows them to process their trauma without withdrawing – whether physically or emotionally – from treatment.

How is recreational use different from MDMA-assisted psychotherapy?
The positive results so far doesn’t mean a person with PTSD should use MDMA as a treatment tool outside of a therapeutic setting. Since the drug can dredge up old trauma, people who pop ecstasy recreationally may end up feeling worse while high instead of euphoric. Feelings of anxiety and self-harm can increase. They’ll then tend to suppress those emotions that were stirred up while partying – at least, that’s what Dr. Mithoefer has seen with patients in his private practice. “And that’s problematic,” he said.

The mindset of the person using MDMA makes all the difference. People who’ve participated in the phase-two trials took the drug while in the care of professionals. They underwent eight-hour therapy sessions that switched between talking and introspection. The physicians, Dr. Mithoefer said, didn’t press when the person under treatment would express their feelings; they let them process their trauma however it unfolded. In a therapeutic setting, people are prepared to deal with the difficult feelings that come up. “It’s not that MDMA makes it easy,” he says. “MDMA makes it possible.”

What are the side effects?
MDMA is not devoid of adverse side effects. According to the National Institute on Drug Abuse, people high on MDMA may experience nausea, muscle tension, increased appetite, sweating and chills, blurred vision and raised body temperature. Some of the more serious – and potentially fatal – risks include dehydration, high blood pressure, heart failure, kidney failure, and an irregular heartbeat.

While infrequent, people have died from recreational ecstasy use – most recently at the Hard Summer rave in Fontana, Califoria. Dr. Mithoefer said the most common cause of MDMA-related fatality is dehydration and heat stroke from “dancing all night in hot conditions without enough fluids.” In rare occasions, he added, some people have passed away from drinking too much water, cause the brain to swell.

Since MDMA elevates blood pressure and pulse, researchers had screened phase two trial participants for underlying cardiac conditions. That’s because a person with heart disease is more likely to have a potentially fatal stroke or heart attack. “Every drug has risks as well as benefits,” Dr. Mithoefer said. “Just because it’s been used in a controlled setting doesn’t mean [MDMA] can’t have risks.”

Where does research go from here?
Researchers anticipate that the FDA will approve the phase three protocol early next year. The phase three trials are then expected to begin this coming summer, with sites across the United States and Canada, and last at least three years. They hope to enroll at least 230 participants.

“I’m hopeful, because we’ve had very strong results in phase two, that we’ll have also strong results in phase 3,” he says.

If, in the end, the FDA and DEA do approve MDMA for therapeutic use, researchers recommend that it only be offered in licensed clinics where trained professionals can safely and effectively manage the drug. Similarly, Dr. Mithoefer notes, to how methadone is administered. “We think that would be the wisest way to do this,” he says.  

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